The overall objective of this proposal is to elucidate the molecular mechanisms involved in the induction, synthesis, and assembly of plasma proteins made in the liver. Particular emphasis will be directed toward two plasma proteins whose synthesis increases as a result of acute inflammatory reactions--fibrinogen and haptoglobin. Primary hepatocyte cultures from fetus and adult rats will be used as a model tissue culture system for investigating the processes of induction, for identifying the inducing factor(s), and studying the molecular processes that signal the increased synthesis of these proteins. Pilot experiments indicate that serum from animals stimulated by turpentine injection into an acute inflammatory state contains substances which markedly enhance fibrinogen synthesis in the hepatocyte tissue culture system. Sensitive quantitative immunological assays will also be employed to elucidate how the multi-chained proteins of fibrinogen and haptoglobin are assembled into intact functional molecules. Particular emphasis will be placed on identifying subunit assemblies which may give insight into how nonidentical polypeptides come together to form functional molecules. Inherent in the goals of this proposal is a continual refinement of the hepatocyte culture system as a useful model for studying the biosynthesis of important liver proteins.